Distribution Of Biosynthetic Gene Clusters Research Articles

Comprehensive analysis of genomic variation, pan-genome and biosynthetic potential of Corynebacterium glutamicum strains.

Corynebacterium glutamicum is a non-pathogenic species of the Corynebacteriaceae family. It has been broadly used in industrial biotechnology for the production of valuable products. Though it is widely accepted at the industrial level, knowledge about the genomic diversity of the strains is limited. Here, we investigated the comparative genomic features of the strains and pan-genomic characteristics. We also observed phylogenetic relationships among the strains based on average nucleotide identity (ANI). We found diversity between strains at the genomic and pan-genomic levels. Less than one-third of the C. glutamicum pan-genome consists of core genes and soft-core genes. Whereas, a large number of strain-specific genes covered about half of the total pan-genome. Besides, C. glutamicum pan-genome is open and expanding, which indicates the possible addition of new gene families to the pan-genome. We also investigated the distribution of biosynthetic gene clusters (BGCs) among the strains. We discovered slight variations of BGCs at the strain level. Several BGCs with the potential to express novel bioactive secondary metabolites have been identified. Therefore, by utilizing the characteristic advantages of C. glutamicum, different strains can be potential applicants for natural drug discovery.

Diversity and distribution of biosynthetic gene clusters in agricultural soil microbiomes.

Bacterial secondary metabolites serve as an important source of molecules for drug discovery. They also play an important function in mediating the interactions of microbial producers with their living environment and surrounding organisms. However, little is known about the genetic novelty, distribution, and community-level impacts of soil bacterial biosynthetic potential on a large geographic scale. Here, we constructed the first catalog of 11,149 biosynthetic gene clusters (BGCs) from agricultural soils across China and unearthed hidden biosynthetic potential for new natural product discovery from the not-yet-cultivated soil bacteria. Notably, we revealed soil pH as the strongest environmental driver of BGC biogeography and predicted that soil acidification and global climate change could damage the biosynthetic potential of the soil microbiome. The co-occurrence network of bacterial genomes revealed two BGC-rich species, i.e., Nocardia niigatensis from Actinobacteriota and PSRF01 from Acidobacteriota, as the module hub and connector, respectively, indicating their keystone positions in the soil microbial communities. We also uncovered a dominant role of BGC-inferred biotic interactions over environmental drivers in structuring the soil microbiome. Overall, this study achieved novel insights into the BGC landscape in agricultural soils of China, substantially expanding our understanding of the diversity and novelty of bacterial secondary metabolism and the potential role of secondary metabolites in microbiota assembly.IMPORTANCEBacterial secondary metabolites not only serve as the foundation for numerous therapeutics (e.g., antibiotics and anticancer drugs), but they also play critical ecological roles in mediating microbial interactions (e.g., competition and communication). However, our knowledge of bacterial secondary metabolism is limited to only a small fraction of cultured strains, thus restricting our comprehensive understanding of their diversity, novelty, and potential ecological roles in soil ecosystems. Here, we used culture-independent metagenomics to explore biosynthetic potentials in agricultural soils of China. Our analyses revealed a high degree of genetic diversity and novelty within biosynthetic gene clusters in agricultural soil environments, offering valuable insights for biochemists seeking to synthesize novel bioactive products. Furthermore, we uncovered the pivotal role of BGC-rich species in microbial communities and the significant relationship between BGC richness and microbial phylogenetic turnover. This information emphasizes the importance of biosynthetic potential in the assembly of microbial communities.

Uncovering the diversity and distribution of biosynthetic gene clusters of prochlorosins and other putative RiPPs in marine Synechococcus strains.

Genome mining studies have revealed the remarkable combinatorial diversity of ribosomally synthesized and post-translationally modified peptides (RiPPs) in marine bacteria, including prochlorosins. However, mining strategies also prove valuable in investigating the genomic landscape of associated genes within biosynthetic gene cluster (BGC) specific to targeted RiPPs of interest. Our study contributes to the enrichment of knowledge regarding prochlorosin diversity. It offers insights into potential mechanisms involved in their biosynthesis and modification, such as hyper-modification, which may give rise to active lantibiotics. Additionally, our study uncovers putative novel promiscuous post-translational enzymes, thereby expanding the chemical space explored within the Synechococcus genus. Moreover, this research extends the applications of mining techniques beyond the discovery of new RiPP-like clusters, allowing for a deeper understanding of genomics and diversity. Furthermore, it holds the potential to reveal previously unknown functions within the intriguing RiPP families, particularly in the case of prochlorosins.

Species-specificity of the secondary biosynthetic potential in Bacillus.

Although Bacillus species have produced a wide variety of structurally diverse and biologically active natural products, the secondary biosynthetic potential of Bacillus species is widely underestimated due to the limited number of biosynthetic gene clusters (BGCs) in this genus. The significant variation in the diversity and novelty of BGCs across different species within the Bacillus genus presents a major obstacle to the efficient discovery of novel natural products from Bacillus. In this study, the number of each class of BGCs in all 6,378 high-quality Bacillus genomes was predicted using antiSMASH, the species-specificity of BGC distribution in Bacillus was investigated by Principal component analysis. Then the structural diversity and novelty of the predicted secondary metabolites in Bacillus species with specific BGC distributions were analyzed using molecular networking. Our results revealed a certain degree of species-specificity in the distribution of BGCs in Bacillus, which was mainly contributed by siderophore, type III polyketide synthase (T3PKS), and transAT-PKS BGCs. B. wiedmannii, B. thuringiensis, and B. cereus are rich in RiPP-like and siderophore BGCs, but lack T3PKS BGCs, while B. amyloliquefaciens and B. velezensis are abundant in transAT-PKS BGCs. These Bacillus species collectively encode 77,541 BGCs, with NRPS and RiPPs being the two most dominant types, which are further categorized into 4,291 GCFs. Remarkably, approximately 54.5% of GCFs and 93.8% of the predicted metabolite scaffolds are found exclusively in a single Bacillus species. Notably, B. cereus, B. thuringiensis, and B. velezensis exhibit the highest potential for producing species-specific NRPS and PKS bioinformatic natural products. Taking two species-specific NRPS gene clusters as examples, the potential of Bacillus to synthesize novel species-specific natural products is illustrated. This study highlights the species-specificity of the secondary biosynthetic potential in Bacillus and provides valuable insights for the targeted discovery of novel natural products from this genus.

Meta-analysis of metagenomics reveals the signatures of vaginal microbiome in preterm birth

Preterm birth (PTB) is the main cause of perinatal incidence rate and mortality worldwide and seriously threatens lives of newborns. In order to improve the understanding of PTB etiology, this study aimed to investigate associations between vaginal microbiome and PTB. We conducted an in-depth meta-analysis on publicly available shotgun metagenomics datasets of vaginal microbiome, including comparisons of microbial composition, metabolic pathways, biosynthetic gene clusters (BGCs), and virulence factors (VFs) between PTB and Healthy groups. Our results showed that 113 species existed in PTB group and 161 species in Healthy group, and their species compositions were significantly different. PTB group was associated with six species, namely Lactobacillus crispatus, Atopobium vaginae, Prevotella bivia, Neisseria subflava, Corynebacterium sp. HMSC078H07 and Capnocytophaga leadbetteri. Between the two groups exhibited 314 significantly different KEGG orthologys. The distribution of BGCs in PTB group were significantly different from that in Healthy group. The total amount of BGCs in PTB group was 95 and they were divided into 12 types, in Healthy group 300 BGCs into 16 types. We also obtained 7080 types of VF genes in PTB group, and 10,748 in Healthy group. The virulence gene with the highest proportion in both groups was ssrA. To conclude, this meta-analysis indicated that significant differences of microbial relative abundance were observed between PTB and Healthy groups. PTB group carried less total amount and types of BGCs, and less types of VFs than those in Healthy group, and PTB group showed significantly different metabolic pathways from Healthy group. We also provided new hypotheses related to vaginal microbiome and PTB.

Distribution of biosynthetic gene clusters for complestatin and related compounds in Streptomyces spp.

Aim. In current work we have analyzed 2664 genomes of Streptomyces spp. (publically available from GenBank) searching for complestatin-like biosynthetic gene clusters (BGCs). Then we aimed to reconstruct in silico putative biosynthetic pathways, encoded within these BGCs, estimating the chemical variability of complestatin-like compounds from natural sources. Methods. Widely accepted genome-mining tools and approaches for phylogenetic reconstruction were utilized in this work. Results. 53 genomes of Streptomyces spp. were found to contain complestatin-like BGCs, although only 33 BGCs were found within one contig – others were partial or highly fragmented. Reconstruction of multi-locus phylogeny for 33 found BGCs and complestatin BGC allowed to divide all these BGCs into five phylogenetic subgroups. Representatives of each subgroup exhibited characteristic organization of corresponding BGCs. Reconstruction of putative biosynthetic pathways allowed us to predict that discovered BGCs might potentially code the biosynthesis of new complestatin derivatives: norcomplestatin, N-malonyl-norcomplestatin, and N-acetyl-norcomplestatin. Conclusions. Complestatin-like BGCs are widely distributed among Streptomyces spp. and might encode novel complestain derivatives, which merits further experimental investigation.

Genome mining of biosynthetic gene clusters intended for secondary metabolites conservation in actinobacteria

Evolution of genome sequencing technology, on the one hand, and advancement of computational genome mining tools, on the other hand, paves way for improvement in predicting secondary metabolites. In past, numerous efforts were made concerning genome mining for recognizing secondary metabolites within the genus, but only a negligible quantity of comparative genomic reports had carried out among species of different genera. In this study, we explored potential of 24 actinobacteria species belonging to the genera, including Streptomyces, Nocardia, Micromonospora, and Saccharomonospora, to traverse diversity and distribution of Biosynthetic Gene Clusters (BGCs). Investigating results obtained from antiSMASH (Antibiotics and Secondary Metabolites Analysis Shell), NaPDoS (Natural Product Domain Seeker), and NP.searcher revealed conservation of genus-specific gene clusters among various species. E.g., NAGGN (n-acetyl glutaminyl glutamine amide) is present in Micromonospora, furan in Nocardia, melanin, and lassopeptide occur in Streptomyces. Bioactive compounds like alkyl-O-dihydro geranyl methoxy hydroquinone, SapB, desferrioxamine E, 2-Methylisoborneol, mayamycin, cyclodipeptide synthase, diisonitrile, salinichelin, hopene, ectoine and isorenieratene are highly conserved among diverse genera. Furthermore, pharmacological activity of actinobacterial derived metabolites against bacterial and fungal pathogens were illustrated. We need to accomplish large-scale analysis of natural products, including various genera of actinobacteria to deliver comprehensive intuition to overcome antibiotic resistance.

Phages carry interbacterial weapons encoded by biosynthetic gene clusters

Bacteria produce diverse specialized metabolites that mediate ecological interactions and serve as a rich source of industrially relevant natural products. Biosynthetic pathways for these metabolites are encoded by organized groups of genes called biosynthetic gene clusters (BGCs). Understanding the natural function and distribution of BGCs provides insight into the mechanisms through which microorganisms interact and compete. Further, understanding BGCs is extremely important for biocontrol and the mining of new bioactivities. Here, we investigated phage-encoded BGCs (pBGCs), challenging the relationship between phage origin and BGC structure and function. The results demonstrated that pBGCs are rare, and they predominantly reside within temperate phages infecting commensal or pathogenic bacterial hosts. Further, the vast majority of pBGCs were found to encode for bacteriocins. Using the soil- and gut-associated bacterium Bacillus subtilis, we experimentally demonstrated how a temperate phage equips a bacterium with a fully functional BGC, providing a clear competitive fitness advantage over the ancestor. Moreover, we demonstrated a similar transfer of the same phage in prophage form. Finally, using genetic and genomic comparisons, a strong association between pBGC type and phage host range was revealed. These findings suggest that bacteriocins are encoded in temperate phages of a few commensal bacterial genera. In these cases, lysogenic conversion provides an evolutionary benefit to the infected host and, hence, to the phage itself. This study is an important step toward understanding the natural role of bacterial compounds encoded by BGCs, the mechanisms driving their horizontal transfer, and the sometimes mutualistic relationship between bacteria and temperate phages.

Complete genome sequence of Bacillus velezensis NST6 and comparison with the species belonging to operational group B. amyloliquefaciens

Bacillus spp. play important roles in production of bioactive natural products with potential agricultural and medical applications. The three families of lipopeptides produced by Bacillus spp. have been most recognized for their antagonistic activity against other microbes, i.e. fengycin, iturin, and surfactin. A novel strain NST6 was isolated from soil and identified as B. velezensis based on phylogenomic analysis. Genome analysis revealed 21 putative biosynthetic gene clusters including the ones responsible for producing bacillomycin and surfactin. However, fengycin cluster was compromised with absence or partial disruption of three non-ribosomal peptide synthetases. Distribution of biosynthetic gene clusters showed that clusters for iturin families were well conserved in 327 genomes of the species belonging to the operational group B. amyloliquefaciens. However, clusters for fengycin and surfactin showed dynamic distribution at gene level. Comparative analysis of closely related species would provide new insights to the diversity in genetic elements for secondary metabolites.

Identification of Secondary Metabolite Gene Clusters in the Pseudovibrio Genus Reveals Encouraging Biosynthetic Potential toward the Production of Novel Bioactive Compounds.

Increased incidences of antimicrobial resistance and the emergence of pan-resistant ‘superbugs’ have provoked an extreme sense of urgency amongst researchers focusing on the discovery of potentially novel antimicrobial compounds. A strategic shift in focus from the terrestrial to the marine environment has resulted in the discovery of a wide variety of structurally and functionally diverse bioactive compounds from numerous marine sources, including sponges. Bacteria found in close association with sponges and other marine invertebrates have recently gained much attention as potential sources of many of these novel bioactive compounds. Members of the genus Pseudovibrio are one such group of organisms. In this study, we interrogate the genomes of 21 Pseudovibrio strains isolated from a variety of marine sources, for the presence, diversity and distribution of biosynthetic gene clusters (BGCs). We expand on results obtained from antiSMASH analysis to demonstrate the similarity between the Pseudovibrio-related BGCs and those characterized in other bacteria and corroborate our findings with phylogenetic analysis. We assess how domain organization of the most abundant type of BGCs present among the isolates (Non-ribosomal peptide synthetases and Polyketide synthases) may influence the diversity of compounds produced by these organisms and highlight for the first time the potential for novel compound production from this genus of bacteria, using a genome guided approach.

Microbiome: Commensally sourced antibiotics.

A new study analyses the distribution of biosynthetic gene clusters in the human microbiome and finds a novel bacterial thiopeptide with antibacterial properties.